Alpadopar: Uses, Dosage Side Effect and Composition

Description and Composition of Alpadopar

Alpadopar is a phenylalanine derivative and an aromatic amino acid decarboxylase inhibitor with antihypertensive activity. It contains methyldopa as its active pharmaceutical ingredient and other excipients in sufficient quantities. It is a prodrug that is metabolized in the central nervous system into alpha-methylnorepinephrine, a potent alpha-2 adrenergic agonist.

Mechanism of Actions and Pharmacology of Alpadopar

How does methyldopa work?

The exact mechanism of antihypertensive action of methyldopa is unknown. However, it is thought to involve stimulation of central alpha-adrenergic receptors by a metabolite, alpha-methylnorepinephrine, thus inhibiting sympathetic outflow to the heart, kidneys and peripheral vasculature. Reduced peripheral resistance and plasma renin activity levels may also contribute to its effect.

Pharmacokinetics of Alpadopar

Absorption:

Absorption of methyldopa from the gastrointestinal tract is variable but averages approximately 50%.

Protein Binding:

Methyldopa – Low (less than 20%)

Its sulphate conjugate – Moderate

Biotransformation:

It is extensively metabolised and is converted to alpha-methyinorepinephrine in central adrenergic neurons; methyldopate hydrochloride is hydrolysed to methyldopa.

Sulphate conjugation occurs to a greater extent after orat than after intravenous administration

Half-life:

Normal – Alpha: 1.7 hours

Anuric – Alpha: 3.6 hours

Time to peak effect:

Single dose – 4 to 6 hours

Multiple doses – 2 to 3 days

Duration of action:

Single dose – 12 to 24 hours

Multiple doses – 24 to 48 hours

Excretion:

Renal, approximately 70% of absorbed drug is excreted in urine as methyldopa and its mono-O-sulfate metabolite.

Unabsorbed oral methyldopa is excreted unchanged in the feces

Indications and Uses of Alpadopar

Methyldopa is used in treatment of:

  1. Moderate to severe hypertension.
  2. Gestational hypertension (or pregnancy-induced hypertension)
  3. Pre-eclampsia

Contraindication of Alpadopar

When should one not take methyldopa?

Not recommended for patients with acute liver disease or phaeochromocytoma

Precautions

  • Evidence of hemolytic anaemia is an indication for discontinuing the drug.
  • Positive Coombs’ tests may indicate an incompatible cross-match when transfusion is required and an indirect Coombs test should be carried out
  • Safety for use in pregnancy and lactation has not been established.
  • Caution if any kind of surgery or dialysis is required.

Pregnancy and Lactation

Is methyldopa to be taken in pregnancy or by breastfeeding women?

Safety for use in pregnancy and lactation has not been established. It is however used after first trimester in the treatment of pregnancy induced hypertension and preeclampsia.

Side Effects of Alpadopar

What are the side effects of methyldopa?

  • Drowsiness
  • Edema
  • Dry mouth
  •  Geadache.

Other side effects other than those listed above can occur.

Report to your healthcare provider if you experience severe side effects while taking this drug.

Drug Interactions

Concurrent use with the following drugs is not recommended.

  • Monoamine oxidase (MAO) inhibitors,
  • Levodopa
  • Methotrimeprazine.

Concurrent use with the following drugs requires careful monitoring

  • Alcohol,
  • Antihypertensives
  • General anaesthetics
  • Norepinephrine.

Overdosage

Clinical features:

  • Dizziness
  • Drowsiness
  • Hypotension
  • Tachycardia or bradycardia,
  • Hypothermia
  • Extra-pyramidal signs
  • Coma.

Treat overdosage by emesis or gastric lavage, if appropriate; and IV 1-2 mg benztropine if extrapyramidal signs are present

Dosage and Adminstration

What is the dosage of methyldopa?

Adults:

Initial – Oral, 250 mg two or three times a day for two days, the dosage then being adjusted as directed.

Maintenance – Oral, 500 mg to 2 g a day, divided into two to four doses, not exceeding 3 g daily.

Children:

Oral, initially 10 mg per kg of body weight daily, divided into two to four doses, the dosage then being adjusted as directed, not exceeding 65 mg per kg of body weight or 3 g daily, whichever is less.

 

Chemical structure of alpadopar

 

Storage

Store below 25°C. Protect from light. Keep all medicines away from the reach of children.

References

  1. https://pubchem.ncbi.nlm.nih.gov/compound/methyldopa
  2. Dopatab drug leaflet: Hovid brand of methyldopa
  3. https://www.sciencedirect.com/topics/neuroscience/methyldopa